Elucidation and regulation of the mechanism underlying female reproductive tract diseases by targeting adult stem cells

• Project/Area Number: 20249067
• Research Category: Grant-in-Aid for Scientific Research (A)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Obstetrics and gynecology
• Research Institution: Keio University
• Principal Investigator: YOSHIMURA Yasunori Keio University, 医学部, 教授 (10129736)
• Co-Investigator(Kenkyū-buntansha): MARUYAMA Tetsuo 慶應義塾大学, 医学部, 講師 (10209702) ; UCHIDA Hiroshi 慶應義塾大学, 医学部, 助教 (90286534) ; 梶谷 宇 慶應義塾大学, 医学部, 助教 (60407111)
• Project Period (FY): 2008 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥50,180,000 (Direct Cost: ¥38,600,000、Indirect Cost: ¥11,580,000); Fiscal Year 2010: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000); Fiscal Year 2009: ¥7,540,000 (Direct Cost: ¥5,800,000、Indirect Cost: ¥1,740,000); Fiscal Year 2008: ¥37,050,000 (Direct Cost: ¥28,500,000、Indirect Cost: ¥8,550,000)
• Keywords: 再生医学 / 移植・再生医療 / 応用動物 / 細胞・組織 / マイクロアレイ / 幹細胞

Research Abstract

The aim of this research project was to elucidate the mechanism underlying the female reproductive tract diseases and to develop novel therapeutic strategies by targeting adult stem cells. We have developed a novel method to isolate and characterize human myometrial stem cells and demonstrated their involvement in the pregnancy-induced uterine remodeling. We also have isolated and characterized human endometrial stem cells thereby proposing stem cell theory not only for the mechanism underlying physiological endometrial regeneration but also for the pathogenesis of endometriosis.

Research Products

• [Journal Article] ミニ・シンポジウム2「子宮内膜幹細胞と子宮内膜症」 (2011)
  • Author(s): 丸山哲夫
  • Journal Title: 第1回Asian Conference on Endometriosis Mini-symposium : Endometriosisi reseach in Japan Prog.Med.別刷り Volume: 31 Pages: 621-628
• [Journal Article] Stem Cell-Like Properties of the Endometrial Side Population : Implication in Endometrial Regeneration. (2010)
  • Author(s): Masuda H, Matsuzaki Y, Hiratsu E, Ono M, Nagashima T, Kajitani T, Arase T, Oda H, Uchida H, Asada H, Ito M, Yoshimura Y, Maruyama T, Okano H
  • Journal Title: PLoS ONE. 5(4)
  • Peer Reviewed
• [Journal Article] Stem/progenitor cells and the regeneration potentials the human uterus. (2010)
  • Author(s): 丸山哲夫
  • Journal Title: Reprod Med Biol. 9 Pages: 9-16
  • NAID: 10027049934
  • Peer Reviewed
• [Journal Article] Xenografted human amniotic membrane-derived mesenchymal stem cells are immunologically tolerated and transdifferentiated into cardiomyocytes. (2010)
  • Author(s): Tsuji H, Miyoshi S, Ikegami Y, Hida N, Asada H, Togashi I, Suzuki J, Satake M, Nakamizo H, Tanaka M, Mori T, Segawa K, Nishiyama N, Inoue J, Makino H, Miyado K, Ozawa S, Yoshimura Y, Umezawa A
  • Journal Title: Circ Res. 106 Pages: 1613-1623
  • Peer Reviewed
• [Journal Article] Involvement of a novel preimplantation-specific gene encoding the high mobility group box protein Hmgpi in early embryonic development. (2010)
  • Author(s): Yamada N, Hamatani Y, Akutsu H, Chikazawa N, Kuji N, Yoshimura Y, Umezawa A
  • Journal Title: Hum Mol Genet. 19 Pages: 480-493
  • Peer Reviewed
• [Journal Article] Xenografted human amniotic membrane-derived mesenchymal stem cells are immunologically tolerated and transdifferentiated into cardiomyocytes. (2010)
  • Author(s): Tsuji H, Yoshimura Y, et al
  • Journal Title: Circ Res. Volume: 106 Pages: 1613-1623
  • Peer Reviewed
• [Journal Article] Involvement of a novel preimplantation-specific gene encoding the high mobility group box protein Hmgpi in early embryonic development. (2010)
  • Author(s): Yamada M, Yoshimura Y, et al.
  • Journal Title: Hum Mol Genet. Volume: 19 Pages: 480-493
  • Peer Reviewed
• [Journal Article] OCT4 expression in human uterine myometrial stem/progenitor cells. (2010)
  • Author(s): Ono M, Yoshimura Y, et al.
  • Journal Title: Hum Reprod. Volume: 25 Pages: 2059-2067
  • Peer Reviewed
• [Journal Article] Human uterine stem/progenitor cells : their possible role in uterine physiology and pathology. (2010)
  • Author(s): Maruyama T, Yoshimura Y, et al.
  • Journal Title: Reproduction. Volume: 140 Pages: 11-22
  • Peer Reviewed
• [Journal Article] Stem Cell-Like Properties of the Endometrial Side Population : Implication in Endometrial Regeneration. (2010)
  • Author(s): Masuda H, Yoshimura Y, et al.
  • Journal Title: PLoS ONE. Volume: 5
  • Peer Reviewed
• [Journal Article] Stem/progenitor cells and the regeneration potentials the human uterus. (2010)
  • Author(s): Maruyama T
  • Journal Title: Reprod Med Biol. Volume: 9 Pages: 9-16
  • NAID: 10027049934
  • Peer Reviewed
• [Journal Article] シンポジウム3「周産期医療と再生医学」産婦人科医療と再生医療ソース・ヒト子宮由来幹細胞 (2010)
  • Author(s): 丸山哲夫
  • Journal Title: 日本周産期・新生児医学会雑誌 Volume: 46 Pages: 1008-1010
• [Journal Article] 子宮における幹細胞 (2010)
  • Author(s): 丸山哲夫
  • Journal Title: 産婦人科の実際 Volume: 59 Pages: 1381-1387
  • NAID: 40017287076
• [Journal Article] ヒト子宮における幹細胞 (2010)
  • Author(s): 丸山哲夫
  • Journal Title: 日本生殖内分泌学会雑誌 Volume: 15 Pages: 25-27
  • NAID: 40017350216
• [Journal Article] 再生医療への応用 (2010)
  • Author(s): 吉村泰典
  • Journal Title: 産婦の実際 Volume: 59 Pages: 2139-2146
• [Journal Article] Hypothalamic dysfunction in a female with isolated hypogonadotropic hypogonadism and compound heterozygous TACR3 mutation and clinical manifestation in her heterozygous mother (2010)
  • Author(s): Fukami M, Maruyama T, Deteki S, Sato N, Yoshimura Y, Ogata T
  • Journal Title: Horm Res Paediatr. 73 Pages: 477-481
  • Peer Reviewed
• [Journal Article] Stem cell-like properties of the endometrial side population : implication in endometrial regeneration (2010)
  • Author(s): Masuda H, Matsuzaki Y, Hiratsu E, Ono M, Nagashima T, Kajitani T, Arase T, Oda H, Uchida H, Asada H, Ito M, Yoshimura Y, Maruyama T, Okano H
  • Journal Title: PLoS ONE. 5
  • Peer Reviewed
• [Journal Article] Therapeutic Strategies for Implantation Failure due to Endometrial Dysfunction. (2009)
  • Author(s): 丸山哲夫
  • Journal Title: J Mamm Ova Res. 26(3) Pages: 129-133
  • NAID: 10026349767
  • Peer Reviewed
• [Journal Article] The UDP-glucose recepter P2RY14 triggers innate mucosal immunity in the female reproductive tract by inducing IL-8. (2009)
  • Author(s): Arase T, Uchida H, Kajitani T, Ono M, TamakiK, Oda H, Nishikawa S, Kagami M, Nagashima T, Masuda H, Asada H, Yoshimura Y, Maruyama T
  • Journal Title: J Immunol.(平成21年度日本産科婦人科学会優秀論文賞) 182(11) Pages: 7074-7084
  • Peer Reviewed
• [Journal Article] Epigenetic Treatment in Assisted Human Embryo Implantation (2009)
  • Author(s): Uchida H, Maruyama T, Kagami M, Oda H, Nishikawa S, Kajitani T, Asada H, Yoshimura Y
  • Journal Title: J.Mamm.Ova Res. 26 Pages: 116-121
  • NAID: 130004436751
  • Peer Reviewed
• [Journal Article] Therapeutic Strategies for Implantation Failure due to Endometrial Dysfunction (2009)
  • Author(s): Maruyama T
  • Journal Title: J.Mamm.Ova Res. 26 Pages: 129-133
  • NAID: 10026349767
  • Peer Reviewed
• [Journal Article] The UDP-glucose recepter P2RY14 triggers innate mucosal immunity in the female reproductive tract by inducing IL-8 (2009)
  • Author(s): Arase T, Uchida H, Kajitani T, Ono M, Tamaki K, Oda H, Nishikawa S, Kagami M, Nagashima T, Masuda H, Asada H, Yoshimura Y, Maruyama T
  • Journal Title: J Immunol. 182 Pages: 7074-7084
  • Peer Reviewed
• [Journal Article] Prenatal diagnosis of retroperitoneal teratoma : a case report and review of the literature. (2009)
  • Author(s): Asai S, Ishimoto H, Kim SH, Higuchi T, Minegishi K, Tanaka M, Hoshino K, Morikawa Y, Yoshimura Y
  • Journal Title: Fetal Diagn Ther 25 Pages: 76-78
  • Peer Reviewed
• [Journal Article] The UDP-glucose receptor P2RY14 triggers innate mucosalimmunity in the female reproductive tract by inducing IL-8. (2009)
  • Author(s): Arase T, Uchida H, Kajitani T, Ono M, Tamaki K, Oda H, Nishikawa S, Kagami M, Nagashima T, Masuda H, Asada H, Yoshimura Y, Maruyama T
  • Journal Title: The Journal of Immunology (In press)
  • Peer Reviewed
• [Journal Article] Molecular and cellular mechanisms for defferentiation and regeneration of the uterine endometrium. (2008)
  • Author(s): 丸山哲夫, 吉村泰典
  • Journal Title: Endocrine J. 55(5) Pages: 795-810
  • Peer Reviewed
• [Journal Article] In vivo Imaging in Humanized Mice. (2008)
  • Author(s): Masuda H, Okano. J.H, Maruyama T, Yoshimura Y, Okano H, Matsuzaki Y
  • Journal Title: Current Topics in Microbiology and Immunology 324 Pages: 179-196
  • Peer Reviewed
• [Journal Article] Activation of SRC kinase and phosphorylation of STAT5 are required for decidual transformation of human endometrial stromal cells. (2008)
  • Author(s): Nagashima T, Maruyama T, Uchida H, Kajitani T, Arase T, Ono M, Oda H, Kagami M, Masuda H, Nishikawa S, Asada H, Yoshimura Y
  • Journal Title: Endocrinology.(平成22年度日本生殖学会学術奨励賞) 149(3) Pages: 1227-1234
  • Peer Reviewed
• [Journal Article] Glycodelin blocks progression to S phase and inhibits cell growth : a possible progesterone-induced regulator for endometrial epithelial cell growth. (2008)
  • Author(s): Ohta K, Maruyama T, Uchida H, Ono M, Nagashima T, Arase T, Kajitani T, Oda H, Morita M, Yoshimura Y
  • Journal Title: Mol Hum Reprod. 14(1) Pages: 17-22
  • Peer Reviewed
• [Journal Article] Regeneration and adult stem cells in the human female reproductive tract. (2008)
  • Author(s): Ono M, Maruyama T, Yoshimura Y
  • Journal Title: Stem Cells and Cloning. 1 Pages: 23-29
  • NAID: 110006958167
  • Peer Reviewed
• [Journal Article] Ureteral catheter placement for prevention of ureteral injury during laparoscopic hysterectomy. (2008)
  • Author(s): Tanaka Y, Asada H, Kuji N, Yoshimura Y
  • Journal Title: J Obstet Gynaecol Res 34 Pages: 67-72
  • NAID: 10021250253
  • Peer Reviewed
• [Journal Article] Analysis of serum FSH bioactivity in a patient with an FSH-secreting pituitary microadenoma and multicystic ovaries : A Case Report. (2008)
  • Author(s): Kajitani T, Liu S, Maruyama T, Uchida H, Sakurai R, Masuda H, Nagashima T, Ono M, Arase T, Yoshimura Y
  • Journal Title: Hum Reprod 23 Pages: 435-439
  • Peer Reviewed
• [Journal Article] Glycodelin inhibits progression to S phase and cell proliferation : a progesterone-induce regulator for endometrial epithelial cell growth. (2008)
  • Author(s): Ota K, Maruyama T, Uchida H, Ono M, Nagashima T, Arase T, Kajitani T, Kagami M, Morita M, Yoshimura Y
  • Journal Title: Mol Hum Reprod 14 Pages: 17-22
  • Peer Reviewed
• [Journal Article] Activation of SRC kinase and phosphorylation of STAT5 are required for decidual transformation of human endometrial stromal cells. (2008)
  • Author(s): Nagashima T, Maruyama T, Uchida H, Kajitani T, Arase T, Ono M, Oda H, Kagami M, Masuda H, Nishikawa S, Arase H, Yoshimura Y
  • Journal Title: Endocrinology 149 Pages: 1227-1234
  • Peer Reviewed
• [Journal Article] In vivo imaging in humanized mice. (2008)
  • Author(s): Masuda H, Okano HJ, Maruyama T, Yoshimura Y, Okano H, Matsuzaki Y
  • Journal Title: Curr Top Microbiol Immunol 324 Pages: 179-196
  • Peer Reviewed
• [Journal Article] The periphery of the human fetal adrenal gland is a site of angiogenesis : Zonal differential expression and regulation of angiogenic factors. (2008)
  • Author(s): Ishimoto H, Minegishi K, Higuchi T, Furuya M, Asai S, Kim SH, Tanaka M, Yoshimura Y, Jaffe RB
  • Journal Title: J Clin Endocrinol Metab 93 Pages: 2402-2408
  • Peer Reviewed
• [Journal Article] Semiquantitative assessment of MR imaging in prediction of efficacy of gonadotropin-releasing hormone agonist for volume reduction of uterine leiomyoma : Initial experience. (2008)
  • Author(s): Okuda S, Oshio K, Shinmoto H, Tanimoto A, Asada H, Fujii T, Yoshimura Y, Kuibayashi S
  • Journal Title: Radiology 248 Pages: 917-924
  • Peer Reviewed
• [Journal Article] Buoyant density and sedimentation dynamics of HIV-1 in two density-gradient media for semen processing. (2008)
  • Author(s): Kuji N, Yoshii T, Hatnatani T, Hanabusa H, Yoshimura Y, Kato S
  • Journal Title: Fertil Steril 90 Pages: 1983-1987
  • Peer Reviewed
• [Journal Article] Pregnancy outcomes of reciprocal translocation carriers who have a history of repeated pregnancy loss. (2008)
  • Author(s): Ozawa N, Maruyama T, Nagashima T, Ono M, Arase T, Ishimoto H, Yoshimura Y
  • Journal Title: Fertil Steril 90 Pages: 1301-1304
  • Peer Reviewed
• [Journal Article] Occipital hemangioma : prenatal sonographic and magnetic resonanee image. (2008)
  • Author(s): Miyakoshi K, Tanaka M, Matsumoto T, Hattori Y, Minegishi K, Ishimoto H, Yoshimura Y
  • Journal Title: J Obstet Gynaecol Res 34 Pages: 666-669
  • Peer Reviewed
• [Journal Article] Molecular and cellular mechanisms for differentiation and regeneration of the uterine endometrium. (2008)
  • Author(s): Maruyama T, Yoshimura Y
  • Journal Title: Endocr J 55 Pages: 795-810
  • NAID: 10024422609
  • Peer Reviewed
• [Journal Article] Regeneration and adult stem cells in the human female reproductive tract. (2008)
  • Author(s): Ono M, Maruyama T, Yoshimura Y
  • Journal Title: Stem Cells and Cloning Pages: 23-29
  • NAID: 110006958167
  • Peer Reviewed
• [Presentation] クローン、幹細胞そしてiPS (2011)
  • Author(s): 吉村泰典
  • Organizer: 金沢大学大学院医学系研究科産科婦人科同門会共催学術講演会
  • Place of Presentation: 石川県(招請講演)
  • Year and Date: 2011-03-05
• [Presentation] いのちの誕生と生殖医療-光と影- (2011)
  • Author(s): 吉村泰典
  • Organizer: 第55回日本生殖医学会(招請講演)
  • Place of Presentation: 徳島県徳島市(招請講演)
• [Presentation] 子宮内膜症の幹細胞説 (2011)
  • Author(s): 丸山哲夫
  • Organizer: 産婦人科スプリングフォーラム
  • Place of Presentation: 京都府京都市・京都平安ホテル(招請講演)
• [Presentation] 子宮内膜症の幹細胞説 (2011)
  • Author(s): 丸山哲夫
  • Organizer: 産婦人科スプリングフォーラム
  • Place of Presentation: 京都府京都市(招請講演)
• [Presentation] Human uterine stem/progenitor cells. Program in Developmental biology (2010)
  • Author(s): Tetsuo Maruyama
  • Organizer: Baylor College of Medicine(BCM).
  • Place of Presentation: Huston, USA(招請講演/セミナー)
  • Year and Date: 2010-10-21
• [Presentation] Human uterine stem/progenitor cells. (2010)
  • Author(s): Tetsuo Maruyama
  • Organizer: Program in Developmental biology, Baylor College of Medicine(BCM).
  • Place of Presentation: Huston, USA
  • Year and Date: 2010-10-21
• [Presentation] 幹細胞からみた子宮内膜症の発症・伸展メカニズム (2010)
  • Author(s): 丸山哲夫
  • Organizer: 第2回婦人科ホルモン依存性疾患研究会
  • Place of Presentation: 東京(招請講演/セッション)
  • Year and Date: 2010-05-08
• [Presentation] 幹細胞からみた子宮内膜症の発症・伸展メカニズム (2010)
  • Author(s): 丸山哲夫
  • Organizer: 第2回婦人科ホルモン依存性疾患研究会
  • Place of Presentation: 東京
  • Year and Date: 2010-05-08
• [Presentation] Possible involvement of endometrial stem/progenitor cells in the pathogenesis of endocetriosis. (2010)
  • Author(s): Tetsuo Maruyama, Hirotaka Masuda, Takashi Nagashima, Takashi Kajitani, Masanori Ono, Sayaka Nishikawa-Uchida Hideyuki Oda, Kaoru Miyazaki, Toru Arase, Maki Kagami, Hiroshi Uchida Hironori Asada, Yasunori Yoshimura
  • Organizer: The First Asian Conference on Endometriosis(ACE).
  • Place of Presentation: Shanghai, China(招請講演)
• [Presentation] Somatic Stem Cells in the myometrium and its putative implication in myoma formation. (2010)
  • Author(s): Tetsuo Maruyama
  • Organizer: 26th European Society of Human Reproduction & Enbryology(ESHRE)
  • Place of Presentation: Rome, Italy(招請講演)
• [Presentation] Possible involvement of endometrial stem/progenitor cells in the pathogenesis of endocetriosis. (2010)
  • Author(s): Tetsuo Maruyama, Yasunori Yoshimura, et al.
  • Organizer: The First Asian Conference on Endometriosis(ACE).
  • Place of Presentation: Shanghai, China(招待講演)
• [Presentation] Prospective isolation and functional analysis of stem/progenitor cells from the human uterine myometrium. (2010)
  • Author(s): Masanori Ono, Yasunori Yoshimura, et al.
  • Organizer: 8th International Society for Stem Cell Research(ISSCR).
  • Place of Presentation: San Francisco, CA USA
• [Presentation] Somatic Stem Cells in the myometrium and its putative implication in myoma formation. (2010)
  • Author(s): Tetsuo Maruyama
  • Organizer: 26th European Society of Human Reproduction & Enbryology(ESHRE).
  • Place of Presentation: Rome, Italy(招待講演)
• [Presentation] いのちの誕生と生殖医療-光と影- (2010)
  • Author(s): 吉村泰典
  • Organizer: 第55回日本生殖医学会
  • Place of Presentation: 徳島県徳島市(招請講演)
• [Presentation] 産婦人科医療と再生医療ソース-ヒト子宮由来幹細胞- (2010)
  • Author(s): 丸山哲夫
  • Organizer: 第46回日本周産期・新生児医学会
  • Place of Presentation: 兵庫県神戸市
• [Presentation] Cell surface marker-based isolation and function and functional analysis of human myometrial stem cells. (2010)
  • Author(s): Masanori Ono, Yasunori Yoshimura, et al.
  • Organizer: 第62回日本産科婦人科学会International Session
  • Place of Presentation: 東京
• [Presentation] Animal model for reconstructed functional human endometrium : Potential for drug testing and gene-target validation. (2009)
  • Author(s): Tetsuo Maruyama
  • Organizer: IUPS Satellite Symposium on Endometrial Receptivity and Blastocyst.
  • Place of Presentation: Kyoto, Japan(招請講演)
  • Year and Date: 2009-07-25
• [Presentation] Animal model for reconstructed function human endometrium : Potential for drug testing and gene-target validation (2009)
  • Author(s): Tetsuo Maruyama
  • Organizer: IUPS Satellite Symposium on Endometrial Receptivity and Blastocyst
  • Place of Presentation: Kyoto, Japan
  • Year and Date: 2009-07-25
• [Presentation] Up-regulation of 5- and 15-lipoxygenases in endometriosis (2009)
  • Author(s): Takashi Kajitani, Tetsuo Maruyama, Hironori Asada, Akiko Yamasaki, Hideyuki Oda, Sayaka Nishikawa, Hiroshi Uchida, Yasunori Yoshimura
  • Organizer: 25th European Society of Human Reproduction and Embryology(ESHRE)
  • Place of Presentation: Amsterdam, Netherlands
• [Presentation] UDP-glucose and its receptor P2RY14 as a novel innate immunity in the female reproductive tract (2009)
  • Author(s): Toru Arase, Tetsuo Maruyama, Hiroshi Uchida, Takashi Kajitani, Sayaka Nishikawa, Hideyuki Oda, Maki Kagami, Hironori Asada, Yasunori Yoshimura
  • Organizer: 29th Ameican Society for Reproductive Immunology(ASRI)
  • Place of Presentation: Orlando, Florida
• [Presentation] The role of uterine smooth muscle stem cells, isolated based on cell surface markers, in myometrial remodeling in the pregnantuterus. (2009)
  • Author(s): Ono M, Maruyama T, Kajitani T, Uchida H, Oda H, Nishikawa S, Kagami M, Arase T, Nagashima T, Masuda H, Morikawa S, Mabuchi Y, Okano H, Matsuzaki Y, Yoshimura Y
  • Organizer: Society for Gynecologic Investigation 56^<th> Annual Meeting
  • Place of Presentation: Glasgow, Scotland
• [Presentation] Regeneration potential of stem cell systems in the human female reproductive tract. (2008)
  • Author(s): Tetsuo Maruyama
  • Organizer: 1st World Congress on Reproductive Biology (WCRB).
  • Place of Presentation: USA,Hawai(招請講演)
• [Presentation] Isolation and functional analysis of putative human endometrialstem/progenitor cells. (2008)
  • Author(s): Masuda H, Maruyama T, 0no M, Nagashima T, Kajitani T, Okano H, Matsuzaki Y, Yoshimura Y
  • Organizer: Annual Meeting of The European of Human Reproduction and Embryology.
  • Place of Presentation: Barcelona, Spain
• [Presentation] Psychosocial stress and mental health status of Japanese couples with a history of repeated pregnancy. (2008)
  • Author(s): Kagami M, Maruyama T, Kozumi T, Arase T, Uchida H, Yoshimura Y
  • Organizer: ASRM 2008 Annual Meeting
  • Place of Presentation: San Francisco, USA
• [Book] 子宮腺筋症・子宮内膜症における最新の動向 (2011)
  • Author(s): 丸山哲夫
  • Publisher: 日本臨牀社
• [Book] Current topics in Microbiology and Immunology Humanized Mice. (2008)
  • Author(s): Masuda H, Okano HJ, Maruyama T, Yoshimura Y, Okano H, Matsuzaki Y
  • Publisher: Springer